American Association for Cancer Research
15357163mct200173-sup-238825_3_supp_6639209_qp0y7p.docx (425.64 kB)

Supplementary Figure 6 from The HPV and p63 Status in Penile Cancer Are Linked with the Infiltration and Therapeutic Availability of Neutrophils

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journal contribution
posted on 2023-04-03, 18:27 authored by Muriel Charlotte Bernhard, Anabel Zwick, Tobias Mohr, Gilles Gasparoni, Oybek Khalmurzaev, Vsevolod Borisovich Matveev, Philine Loertzer, Alexey Pryalukhin, Arndt Hartmann, Carol-Immanuel Geppert, Hagen Loertzer, Heiko Wunderlich, Carsten Maik Naumann, Holger Kalthoff, Kerstin Junker, Sigrun Smola, Stefan Lohse

Supplementary Figure 6


German Research Foundation



Squamous penile cancer displays a rare human papillomavirus (HPV)–associated tumor entity. Investigations on the molecular pathogenesis of HPV-driven penile cancer are impaired by the rareness of clinical specimens and, in particular, are missing relevant cell culture models. Here, we identified in HPV-positive penile cancer cell lines that HPV16 oncoproteins control TP63 expression by modulating critical regulators, while integration into the TP63 open reading frame facilitates oncogene expression. The resulting feed-forward loop leads to elevated p63 levels that in turn enhance the release of the neutrophil-recruiting chemokine CXCL8. Remarkably, elevated CXCL8 amounts lead to the increased surface exposition of the Fc receptor of human IgA antibodies, FcαRI, on neutrophils and correlated with a higher susceptibility to antibody-dependent neutrophil-mediated cytotoxicity (ADCC) using an EGFR-specific IgA2 antibody. IHC staining of tissue microarrays proved that elevated expression of p63 together with neutrophil infiltration were significantly more frequent in HPV-positive penile cancer displaying a higher tumor grade. In summary, we identified a promising marker profile of patients with penile cancer at higher risk for worse prognosis. However, these patients may benefit from immunotherapeutic approaches efficiently engaging neutrophils for tumor cell killing.